Project Summary/Abstract In response to national calls from the Surgeon General, Congress, and NIMH, the proposed research will investigate neural markers of suicidal ideation and behavior in one of the most vulnerable populations at risk for suicide (i.e., youth with a history of child maltreatment). Child maltreatment is robustly related to youth suicidal ideation and behavior; yet, child maltreatment alone is a poor predictor of future suicidal ideation and behavior. Prediction of future suicidal ideation and behavior is critical and may be currently limited by a lack of knowledge regarding neural underpinnings of known risk factors for suicide. Child maltreatment affects functioning in brain regions implicated in emotion regulation. Further, emotion regulation may be a key process underlying suicidal ideation and behavior. The proposed research will prospectively examine network wide functional connectivity in brain networks implicated in emotion regulation as a predictor of suicidal ideation in two independent samples of youth with and without histories of child maltreatment. This work will explore frontolimbic (e.g., dorsolateral prefrontal cortex?amygdala) connectivity during a widely-used emotion regulation task and resting state scan among youth with and without suicidal ideation and child maltreatment histories. Further, this work will examine neural connectivity as a prospective predictor of suicidal ideation. Based on previous research, it is expected that youth with both child maltreatment and suicidal ideation histories will demonstrate weak frontolimbic connectivity compared to youth with either child maltreatment or suicidal ideation histories alone and control youth. Further, it is hypothesized that weak frontolimbic connectivity will prospectively predict suicidal ideation across ~1-2 years across both samples of youth. Here we have the remarkable ability to cross-validate our findings from one sample in an independent sample of youth. Using a combination of experimental lab-based paradigms, functional network connectivity, and an innovative longitudinal, cross-validation of findings, the proposed research offers a substantial advance within the field that almost exclusively has relied on cross-sectional, single informant, retrospective reports of suicidal ideation. Participants from two independent samples (total N = 340 youth ages 8-16; data collection supported by 2 NIMH funded R01s) with a range of child maltreatment and suicidal ideation histories complete a baseline assessment and fMRI scan, are followed prospectively for ~1-2 years, and complete an additional fMRI scan. We will combine traditional connectivity analysis (graph theory) and a cutting-edge data-driven algorithm to cross-validate neural network connectivity findings from baseline and follow-up (~1-2 years). Findings from the current study may identify concrete markers of risk for suicidal ideation and behavior allowing us to significantly improve prospective prediction. Advancing knowledge of neural underpinnings of youth suicide is critical for addressing this significant public health concern. This project directly addresses national calls for action regarding youth suicide and stands to substantially contribute to the field.